Human skeletal muscle aging atlas
Nature Aging. 2024;4(5):727-744. DOI 10.1038/s43587-024-00613-3. PMID 38622407. PMCID PMC11108788.
How to cite
AMA
Kedlian VR, Wang Y, Liu T, Chen X, Bolt L, Tudor C, et al. Human skeletal muscle aging atlas. Nat Aging. 2024;4(5):727-744. doi:10.1038/s43587-024-00613-3APA
Kedlian, V. R., Wang, Y., Liu, T., Chen, X., Bolt, L., Tudor, C., et al. (2024). Human skeletal muscle aging atlas. Nature Aging, 4(5), 727-744. https://doi.org/10.1038/s43587-024-00613-3BibTeX
@article{kedlian2024human,
title = {Human skeletal muscle aging atlas},
author = {Kedlian, V. R. and Wang, Y. and Liu, T. and Chen, X. and Bolt, L. and Tudor, C. and others},
journal = {Nature Aging},
volume = {4},
number = {5},
pages = {727--744},
year = {2024},
doi = {10.1038/s43587-024-00613-3},
pmid = {38622407}
}Skeletal muscle weakens with age, driving frailty and sarcopenia, yet the cellular changes behind it are hard to read because muscle mixes fibers, stem cells, immune cells and vessels, and each ages differently across the human lifespan. Sequencing can name every cell type present, but it discards where those cells sit in the tissue.
The team built a single-cell and single-nucleus atlas of young and aged human intercostal muscle, then used a 15-plex RareCyte protein-imaging panel to check the immune findings directly in intact sections. Aged muscle had turned inflammatory, with immune cells accumulating as vascular cells thinned, and the spatial imaging confirmed that CD4+ and CD8+ T cells rise with age.
Key findings
- A single-cell and single-nucleus atlas spanned the adult muscle lifespan. The study profiled 90,902 cells and 92,259 nuclei from intercostal muscle of 17 donors — 8 young (about 20–40 years) and 9 aged (about 60–75 years) — resolving 40 major cell populations.
- A 15-plex RareCyte panel placed the aging immune shift in intact tissue. On FFPE sections from two young and two aged donors, custom ArgoFluor-conjugated antibodies imaged on the RareCyte Orion gave a protein-level, in-tissue view that agreed with the sequencing: CD4+ and CD8+ T cells increased with age.
- Aging drove a conserved shift toward inflammation. Aged human muscle was enriched for NK, T, B and mast cells and depleted for vascular cells, with pro-inflammatory cytokines rising across stromal populations; an integrated human–mouse atlas of 346,296 cells confirmed shared aging hallmarks.
Orion in the methods
“The stained slides were imaged using the RareCyte Orion platform with seven lasers and pre-processed using RareCyte Artemis 4.0 software, which compensates for channel crosstalk and autofluorescence.”
— Kedlian et al., Nature Aging (2024), Methods, “Immunfluorescence”
Why it matters for Orion users
If you are weighing Orion for a tissue study, look at the job its spatial imaging was given here. The atlas leaned on sequencing to catalog cell types, but sequencing throws away position, and the authors still needed to see immune cells in place as muscle aged. Orion supplied that view: a 15-plex panel of custom ArgoFluor-conjugated antibodies read across whole FFPE sections in a single round, resolving many markers at once without dissociating the tissue. Because the acquisition is single round rather than cyclic, the panel is captured in one pass on a seven-laser instrument, which protects antigen signal on small, precious donor samples, while the Artemis software compensates for channel crosstalk and autofluorescence. That was enough to confirm, at the protein level and in position, that CD4+ and CD8+ T cells accumulate in aged muscle. For your own work the lesson is practical: Orion can serve as the in-tissue, protein-level check alongside sequencing, showing where a population sits rather than only what it expresses.
